Distinct Mutational Profile of Lynch Syndrome Colorectal Cancers Diagnosed under Regular Colonoscopy Surveillance by Aysel Ahadova, Pauline Luise Pfuderer, Maarit Ahtiainen, Alexej Ballhausen, Lena Bohaumilitzky, Svenja Kösegi, Nico Müller, Yee Lin Tang, Kosima Kosmalla, Johannes Witt, Volker Endris, Albrecht Stenzinger, Magnus von Knebel Doeberitz, Hendrik Bläker, Laura Renkonen-Sinisalo, Anna Lepistö, Jan Böhm, Jukka-Pekka Mecklin, Toni T. Seppälä, Matthias Kloor

“…On the molecular level, incident cancers presented with a significantly lower <i>KRAS</i> codon 12/13 (1/23, 4.3% vs. 11/21, 52%; <i>p</i> = 0.0005) and pathogenic <i>TP53</i> mutation frequency (0/17, 0% vs. 7/21, 33.3%; <i>p</i> = 0.0108,) compared to prevalent cancers; 10/17 (58.8%) incident cancers harbored one or more truncating <i>APC</i> mutations, all showing mutational signatures of mismatch repair (MMR) deficiency. …”
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Base editing-mediated one-step inactivation of the Dnmt gene family reveals critical roles of DNA methylation during mouse gastrulation by Qing Li, Jiansen Lu, Xidi Yin, Yunjian Chang, Chao Wang, Meng Yan, Li Feng, Yanbo Cheng, Yun Gao, Beiying Xu, Yao Zhang, Yingyi Wang, Guizhong Cui, Luang Xu, Yidi Sun, Rong Zeng, Yixue Li, Naihe Jing, Guo-Liang Xu, Ligang Wu, Fuchou Tang, Jinsong Li

“…Here, we establish a system of simultaneous inactivation of multiple endogenous genes in zygotes through screening for base editors that can efficiently introduce a stop codon. Embryos with mutations in Dnmts and/or Tets can be generated in one step with IMGZ. …”
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Synthetic refactor of essential genes decodes functionally constrained sequences in yeast genome by Zhenzhen Liang, Zhouqing Luo, Weimin Zhang, Kang Yu, Hui Wang, Binan Geng, Qing Yang, Zuoyu Ni, Cheng Zeng, Yihui Zheng, Chunyuan Li, Shihui Yang, Yingxin Ma, Junbiao Dai

“…The coding sequences were synonymously recoded with all optimal codons to explore the importance of codon choice. …”
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Efficient and error-free correction of sickle mutation in human erythroid cells using prime editor-2 by Anila George, Anila George, Nithin Sam Ravi, Nithin Sam Ravi, Kirti Prasad, Kirti Prasad, Lokesh Panigrahi, Lokesh Panigrahi, Sanya Koikkara, Vignesh Rajendiran, Vignesh Rajendiran, Nivedhitha Devaraju, Nivedhitha Devaraju, Joshua Paul, Aswin Anand Pai, Aswin Anand Pai, Yukio Nakamura, Ryo Kurita, Poonkuzhali Balasubramanian, Saravanabhavan Thangavel, Srujan Marepally, Shaji R. Velayudhan, Shaji R. Velayudhan, Alok Srivastava, Alok Srivastava, Kumarasamypet M. Mohankumar, Kumarasamypet M. Mohankumar

“…Sickle cell anaemia (SCA) is one of the common autosomal recessive monogenic disorders, caused by a transverse point mutation (GAG &gt; GTG) at the sixth codon of the beta-globin gene, which results in haemolytic anaemia due to the fragile RBCs. …”
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Brittle culm 3, encoding a cellulose synthase subunit 5, is required for cell wall biosynthesis in barley (Hordeum vulgare L.) by Baojian Guo, Baojian Guo, Baojian Guo, Xinyu Huang, Xinyu Huang, Xinyu Huang, Jiang Qi, Jiang Qi, Jiang Qi, Hongwei Sun, Hongwei Sun, Hongwei Sun, Chao Lv, Chao Lv, Chao Lv, Feifei Wang, Feifei Wang, Feifei Wang, Juan Zhu, Juan Zhu, Juan Zhu, Rugen Xu, Rugen Xu, Rugen Xu

“…Genetic analysis and map-based cloning revealed that the bc3 mutant was controlled by a single recessive gene and harbored a point mutation in the HvCESA5 gene, generating a premature stop codon near the N-terminal of the protein. Quantitative real-time PCR (qRT-PCR) analysis showed that the HvCESA5 gene is predominantly expressed in the culms and co-expressed with HvCESA4 and HvCESA8, consistent with the brittle culm phenotype of the bc3 mutant. …”
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<i>KRAS, NRAS, BRAF, HER2</i> and MSI Status in a Large Consecutive Series of Colorectal Carcinomas by Aleksandr S. Martianov, Natalia V. Mitiushkina, Anastasia N. Ershova, Darya E. Martynenko, Mikhail G. Bubnov, Priscilla Amankwah, Grigory A. Yanus, Svetlana N. Aleksakhina, Vladislav I. Tiurin, Aigul R. Venina, Aleksandra A. Anuskina, Yuliy A. Gorgul, Anna D. Shestakova, Mikhail A. Maidin, Alexey M. Belyaev, Liliya S. Baboshkina, Aglaya G. Iyevleva, Evgeny N. Imyanitov

“…<i>BRAF</i> mutations were identified in 556/8355 (6.7%) CRCs (codon 600: 510; codons 594–596: 38; codons 597–602: 8). …”
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Induction of Male Sterility by Targeted Mutation of a Restorer-of-Fertility Gene with CRISPR/Cas9-Mediated Genome Editing in <i>Brassica napus</i> L. by Zunaira Farooq, Muhammad Nouman Riaz, Muhammad Shoaib Farooq, Yifan Li, Huadong Wang, Mayra Ahmad, Jinxing Tu, Chaozhi Ma, Cheng Dai, Jing Wen, Jinxiong Shen, Tingdong Fu, Shouping Yang, Benqi Wang, Bin Yi

“…Such as a high non-synonymous/synonymous codon replacement ratio (dN/dS), autonomous gene duplications, and a possible engrossment in fertility restoration. …”
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Generation of a High Number of Healthy Erythroid Cells from Gene-Edited Pyruvate Kinase Deficiency Patient-Specific Induced Pluripotent Stem Cells by Zita Garate, Oscar Quintana-Bustamante, Ana M. Crane, Emmanuel Olivier, Laurent Poirot, Roman Galetto, Penelope Kosinski, Collin Hill, Charles Kung, Xabi Agirre, Israel Orman, Laura Cerrato, Omaira Alberquilla, Fatima Rodriguez-Fornes, Noemi Fusaki, Felix Garcia-Sanchez, Tabita M. Maia, Maria L. Ribeiro, Julian Sevilla, Felipe Prosper, Shengfang Jin, Joanne Mountford, Guillermo Guenechea, Agnes Gouble, Juan A. Bueren, Brian R. Davis, Jose C. Segovia

“…PKDiPSCs were gene edited to integrate a partial codon-optimized R-type pyruvate kinase cDNA in the second intron of the PKLR gene by TALEN-mediated homologous recombination (HR). …”
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Persistent Nonviral Plasmid Vector in Nasal Tissues Causes False-Positive SARS-CoV-2 Diagnostic Nucleic Acid Tests by Ingrid A. Beck, Sheila Styrchak, Leslie Miller, Fred Mast, Vladimir Vigdorovich, Winnie Yeung, Daisy Ko, Alyssa Oldroyd, Samantha Hardy, Song Li, John Houck, Yonghou Jiang, Nicholas Dambrauskas, Catherine Darcey, Andrew Raappana, William Selman, D. Noah Sather, John D. Aitchison, Whitney E. Harrington, Lisa M. Frenkel

“…However, nucleic acids extracted from these nasal swabs amplified DNA regions of the plasmid vector used by the coworkers, including the ampicillin and neomycin/kanamycin resistance genes, the promoter-nucleocapsid junction, and unique codon-optimized regions. Nasal swabs from these individuals tested positive repeatedly, including during isolation. …”
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RNA editing events and expression profiles of mitochondrial protein-coding genes in the endemic and endangered medicinal plant, Corydalis saxicola by Cui Li, Cui Li, Cui Li, Han Liu, Han Liu, Han Liu, Mei Qin, Mei Qin, Mei Qin, Yao-jing Tan, Xia-lian Ou, Xia-lian Ou, Xia-lian Ou, Xiao-ying Chen, Xiao-ying Chen, Xiao-ying Chen, Ying Wei, Ying Wei, Zhan-jiang Zhang, Zhan-jiang Zhang, Ming Lei, Ming Lei, Ming Lei

“…The mt genome of C. saxicola is represented by a circular chromosome which is 587,939 bp in length, with an overall GC content of 46.50%. 40 unique protein-coding genes (PCGs), 22 tRNA genes and three rRNA genes were identified. Codon usage of the PCGs was investigated and 167 simple sequence repeats were identified. …”
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MIELOFIBROSE PÓS-POLICITEMIA VERA COM MUTAÇÃO NO EXON 12: RELATO DE CASO by GZPES Guiao, LA Antunes, JLM Rosa, LF Silva, IM Toni, GCP Furlin, AC Mattos, KBB Pagnano

“…A maioria das mutações de JAK2 ocorre no códon 617 (V617F), em aproximadamente 96% dos casos. …”
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Clinical and electrophysiological features of SCN8A variants causing episodic or chronic ataxiaResearch in context by Hang Lyu, Christian M. Boßelmann, Katrine M. Johannesen, Mahmoud Koko, Juan Dario Ortigoza-Escobar, Sergio Aguilera-Albesa, Deyanira Garcia-Navas Núñez, Tarja Linnankivi, Eija Gaily, Henriette J.A. van Ruiten, Ruth Richardson, Cornelia Betzler, Gabriella Horvath, Eva Brilstra, Niels Geerdink, Daniele Orsucci, Alessandra Tessa, Elena Gardella, Zofia Fleszar, Ludger Schöls, Holger Lerche, Rikke S. Møller, Yuanyuan Liu

“…Findings: Variants associated with chronic progressive ataxia either decreased Na+ current densities and shifted activation curves towards more depolarized potentials (p.Asn995Asp, p.Lys1498Glu and p.Trp1266Cys) or resulted in a premature stop codon (p.Trp937Ter). Three variants (p.Arg847Gln and biallelic p.Arg191Trp/p.Asp1525Tyr) were associated with episodic ataxia causing loss-of-function by decreasing Na+ current densities or a hyperpolarizing shift of the inactivation curve. …”
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DIAGNÓSTICO MOLECULAR DE BETA TALASSEMIA INTERMÉDIA: RELATO DE HETEROZIGOTO COMPOSTO PARA MUTAÇÃO HBB:C.118C>T (CD39) E HBB:C.-138C>T (-88C>T) by VS Ramos, ACM Berti, GA Bernardino, LA Souza-Junior, IS Dias, RD Costa, MF Galera, L Gazarini, E Belini-Júnior

“…Discussão: Na mutação CD39 um códon de parada é gerado impedindo a tradução eficaz do RNAm do gene HBB, o que leva ao fenótipo β0. …”
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A 66 amino acid micro-peptide encoded by long non-coding RNA RP11-119F7.5 was identified in hepatocellular carcinoma by Chengwen He, Zhiyong Liu, Yanan Pang, Yin Jia, Qin Qin, Ruijiao Kong, Hui Zhang, Shanrong Liu

“…We obtained the full length of the four gene sequences from the UCSC database and analyzed the open reading frames by ORF Finder; to determine the translation potential of the four candidate small open reading frames (smORFs), we subcloned a FLAG epitope tag into the C-terminal of the four selected smORFs before the stop codon, and the fusion sequences were then cloned into three different plasmid vectors (pSPT19, pcDNA3.1, and PEGFP-N1). …”
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Evaluation of genome and base editing tools in maize protoplasts by Yannick Fierlej, Yannick Fierlej, Nathanaël M. A. Jacquier, Loïc Guille, Jérémy Just, Emilie Montes, Christelle Richard, Jeanne Loue-Manifel, Nathalie Depège-Fargeix, Antoine Gaillard, Thomas Widiez, Peter M. Rogowsky

“…Phenotypic analysis of base edited mutant maize plants demonstrated that the introduction of a stop codon but not the mutation of a serine predicted to be phosphorylated in the bHLH (basic helix loop helix) transcription factor ZmICEa (INDUCER OF CBF EXPRESSIONa) caused abnormal stomata, pale leaves and eventual plant death two months after sowing.…”
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ABCA4 c.6480-35A>G, a novel branchpoint variant associated with Stargardt disease by María Rodríguez-Hidalgo, María Rodríguez-Hidalgo, Suzanne E. de Bruijn, Zelia Corradi, Kim Rodenburg, Araceli Lara-López, Alicia Valverde-Megías, Almudena Ávila-Fernández, Almudena Ávila-Fernández, Lidia Fernandez-Caballero, Lidia Fernandez-Caballero, Marta Del Pozo-Valero, Marta Del Pozo-Valero, Jordi Corominas, Jordi Corominas, Christian Gilissen, Christian Gilissen, Cristina Irigoyen, Cristina Irigoyen, Frans P. M. Cremers, Carmen Ayuso, Carmen Ayuso, Javier Ruiz-Ederra, Javier Ruiz-Ederra, Susanne Roosing

“…A midigene splice assay in HEK293T cells revealed the inclusion of the last 47 nucleotides of intron 47 creating a premature stop codon and allowed to categorize the variant as moderately severe. …”
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Building a eukaryotic chromosome arm by de novo design and synthesis by Shuangying Jiang, Zhouqing Luo, Jie Wu, Kang Yu, Shijun Zhao, Zelin Cai, Wenfei Yu, Hui Wang, Li Cheng, Zhenzhen Liang, Hui Gao, Marco Monti, Daniel Schindler, Linsen Huang, Cheng Zeng, Weimin Zhang, Chun Zhou, Yuanwei Tang, Tianyi Li, Yingxin Ma, Yizhi Cai, Jef D. Boeke, Qiao Zhao, Junbiao Dai

“…Next, we demonstrate that these genes can be reconstructed individually using synthetic regulatory sequences and recoded open-reading frames with a “one-amino-acid-one-codon” strategy to remain functional. Finally, a synthetic neochromsome with the reconstructed genes is assembled which could substitute chrXIIL for viability. …”
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The collagen type I alpha 1 chain gene is an alternative safe harbor locus in the porcine genome by Guang-ming XIANG, Xiu-ling ZHANG, Chang-jiang XU, Zi-yao FAN, Kui XU, Nan WANG, Yue WANG, Jing-jing CHE, Song-song XU, Yu-lian MU, Kui LI, Zhi-guo LIU

“…After the knock-in of a 2A peptide-green fluorescence protein (2A-GFP) transgene in the last codon of COL1A1 in multiple porcine cells, including porcine kidney epithelial (PK15), porcine embryonic fibroblast (PEF) and porcine intestinal epithelial (IPI-2I) cells, quantitative PCR (qPCR), Western blotting, RNA-seq and CCK8 assay were performed to assess the safety of COL1A1 locus. …”
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Hypo- and Hyper-Virulent <i>Listeria monocytogenes</i> Clones Persisting in Two Different Food Processing Plants of Central Italy by Fabrizia Guidi, Massimiliano Orsini, Alexandra Chiaverini, Marina Torresi, Patrizia Centorame, Vicdalia Aniela Acciari, Romolo Salini, Barbara Palombo, Giorgio Brandi, Giulia Amagliani, Giuditta Fiorella Schiavano, Francesca Romana Massacci, Stefano Fisichella, Marco Di Domenico, Massimo Ancora, Adriano Di Pasquale, Anna Duranti, Cesare Cammà, Francesco Pomilio, Giuliana Blasi

“…All the CC2 carried a full-length <i>inlA</i> while CC9 and CC121 presented a Premature Stop Codon mutation correlated with less virulence. The hypo-virulent clones CC9 and CC121 appeared the most adapted to food-processing environments; however, even the hyper-virulent clone CC2 warningly persisted for a long time. …”
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Q1291H-CFTR molecular dynamics simulations and ex vivo theratyping in nasal epithelial models and clinical response to elexacaftor/tezacaftor/ivacaftor in a Q1291H/F508del patient by Katelin M. Allan, Katelin M. Allan, Katelin M. Allan, Miro A. Astore, Egi Kardia, Egi Kardia, Egi Kardia, Sharon L. Wong, Sharon L. Wong, Sharon L. Wong, Laura K. Fawcett, Laura K. Fawcett, Laura K. Fawcett, Laura K. Fawcett, Jessica L. Bell, Jessica L. Bell, Simone Visser, Po-Chia Chen, Renate Griffith, Adam Jaffe, Adam Jaffe, Adam Jaffe, Sheila Sivam, Orazio Vittorio, Orazio Vittorio, Serdar Kuyucak, Shafagh A. Waters, Shafagh A. Waters, Shafagh A. Waters, Shafagh A. Waters

“…Q1291H CFTR incurs a splicing defect, producing both a normally spliced but mutant mRNA isoform and a misspliced isoform with a premature termination codon, causing nonsense mediated decay. The effectiveness of ETI in restoring Q1291H-CFTR is largely unknown.Methods: We collected clinical endpoint measurements, including forced expiratory volume in 1 s percent predicted (FEV1pp) and body mass index (BMI), and examined medical history. …”
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